The elderly are more susceptible to many infectious diseases, and yet vaccinating this population is less effective when vaccines that are designed for young individuals are used. To design a vaccine that specifically targets an aging immune system it is first necessary to understand how the aging immune response differs from younger individuals when it encounters a pathogen. Using the aging mouse model of tuberculosis we have found that old mice express a transient early resistance to infection that correlates with the rapid presence of CD8 T cells within the lungs. This identifies a previously unrecognized novel immune mechanism in old mice that is clearly absent from the lungs of young mice. Using the low-dose aerosol infection model of tuberculosis we will characterize this CD8 T cell population further by determining the signals that rapidly recruit it to the lungs, and the mechanism by which it mediates early resistance to infection. Finally, we will use vaccine strategies known to elicit antigen specific CD8 T cell responses to mycobacterial antigens to see if these cells can then be detected within the CD8 cell population recruited into the lungs of old mice after infection with M. tuberculosis. Studies will be carried out in a new BSL-3 facility at Colorado State University and will use old wild type and gene-disrupted mice from our existing in-house aging mouse colonies. The technical approaches in the proposed studies will use a combination of flow cytometry, FACS cell sorting, immunohistochemical staining, and real-time PCR, to address the proposed Aims.